title: Endogenous production of reactive oxygen species by the NADPH oxidase complexes is a determinant of γ-glutamyltransferase expression.
abstract: γ-Glutamyltransferase (GGT) plays a significant role in antioxidant defence and participates in the metabolism of glutathione (GSH). The enzyme is up-regulated after acute oxidative stress and during pro-oxidant periods, but the underlying regulatory mechanisms are not well known. The present investigation studied whether the endogenous reactive oxygen species (ROS) level was a determinant for GGT expression. A substantial amount of ROS is produced through the NADPH oxidase (NOX) system and knockdown of p22phox, a sub-unit of NOX1-4, resulted not only in reduced ROS levels but also in reduced GGT expression in human endometrial carcinoma cells. Phorbol-12-myristate-13-acetate (PMA) is an activator of NOX and it was found that PMA treatment of human colon carcinoma cells both increased cellular ROS levels and subsequently up-regulated GGT expression. On the other hand, the NOX inhibitor apocynin reduced ROS levels as well as GGT expression. The GGT mRNA sub-type A was increased after PMA-induced NOX activation. These results demonstrate that ROS generated from NOX enzymes are a significant determinant for GGT expression and activity.
authors.affiliation: Tumor Biology Research Group, Faculty of Health Sciences, University of Tromsø, Norway.
authors.forename: Chandra
authors.initials: C
authors.lastname: Ravuri
authors.forename: Gunbjørg
authors.initials: G
authors.lastname: Svineng
authors.forename: Serhiy
authors.initials: S
authors.lastname: Pankiv
authors.forename: Nils-Erik
authors.initials: NE
authors.lastname: Huseby
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D017382:Reactive Oxygen Species; C016658:phorbolol myristate acetate; C056165:acetovanillone; D019255:NADPH Oxidases; C086986:CYBA protein, human; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate